Do trypanosomes control mRNA export?
Metabolism, Biochemistry and Genetics of Microorganisms
Final Report Abstract
In eukaryotes, transcription and translation are separated by the nuclear envelope and all newly transcribed mRNAs must pass the nuclear pores to reach the cytoplasm. Importantly, the export of immature mRNAs must be prevented. How exactly this export control is achieved is still not entirely understood, not even in the model systems yeast and human. Trypanosomes are evolutionary very distant to yeast and human and can serve as models to understand conserved and not conserved aspects of this important control system, and contribute to a better understanding of eukaryogenesis. In this project, we set out to identify conserved and trypanosome-unique components that have the potential to function in mRNA export control. We ruled out an involvement of the exon junction complex, that would have been a good candidate as a marker of successful transsplicing. We combined expansion microscopy with proximity labelling and provide a detailed map of the trypanosome nuclear pore complex and all associated proteins, such as transporters and regulatory proteins. We defined new asymmetric components that are mostly trypanosome unique and likely define directionality of transport. We identify many novel proteins that are specific to the nuclear site of the pore, all trypanosome unique but three have structural homology to known export control proteins of yeast and human (TREX-2). We have generated a range of mutants to better understand, how the export system is connected to the pore and how mRNAs are loaded and released from the transport system. We have now defined all components that are localised at the nuclear pore and we start to understand how these are connected to each other. The next step now is the functional characterisation by reverse genetics, that we have started.
Publications
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Detailed characterisation of the trypanosome nuclear pore architecture reveals conserved asymmetrical functional hubs that drive mRNA export. PLOS Biology, 23(2), e3003024.
Gabiatti, Bernardo Papini; Krenzer, Johanna; Braune, Silke; Krüger, Timothy; Zoltner, Martin & Kramer, Susanne
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Trypanosomes lack a canonical EJC but possess an UPF1 dependent NMD-like pathway. PLOS ONE, 20(3), e0315659.
Gabiatti, Bernardo Papini; Freire, Eden Ribeiro; Odenwald, Johanna; de Freitas Nascimento, Janaina; Holetz, Fabiola; Carrington, Mark; Kramer, Susanne & Zoltner, Martin
